crossing96/oncoscreening huggingface dataset:
Pan-cancer analysis reveals potential immunological and prognostic roles of COA6 in human cancers and preliminary exploration of COA6 in bladder cancer.	BACKGROUND: Cytochrome C oxidase assembly factor 6 (COA6) is significantly involved in the progression of cancer and is aberrantly expressed in disease. Nevertheless, the comprehensive analysis of COA6 using many omics techniques, and its impact on the prognosis and immunological microenvironment of cancer patients, remains unexplored. METHODS: We gathered data from 33 cancer cases and conducted a thorough analysis of abnormalities in COA6 gene expression. This analysis included examining its relevance to disease, its diagnostic and prognostic value, pathway enrichment, the immune microenvironment, its association with immune checkpoints, and its ability to predict patient response to immunotherapy and natural small molecule drugs that target the COA6 protein. Ultimately, we examined the function of COA6 in bladder cancer by in vitro research. RESULTS: Our study revealed significant variations in gene expression and identified COA6 as a potential diagnostic biomarker for cancer. COA6 was also discovered to have a crucial function in pan-cancer involving the tumor microenvironment. COA6 has a strong correlation with well-known immunological checkpoints, including TMB and MSI. Molecular docking identified natural small chemical inhibitors that specifically target the COA6 protein. Ultimately, scientific evidence has verified that suppressing the expression of the COA6 gene hinders the growth and infiltration of bladder cancer cells. CONCLUSIONS: Our study emphasizes the significant potential of COA6 as a predictive and immunotherapeutic response biomarker. This finding may lead to future investigation into the mechanism of tumor infiltration and the therapeutic possibilities of COA6 in cancer.	bladder
Robotic simple cystectomy as a last resort for antibiotic-recalcitrant recurrent urinary tract infections in women.	OBJECTIVE: To report a series of women with antibiotic-recalcitrant recurrent urinary tract infections (rUTI) managed with robotic simple cystectomy and ileal conduit urinary diversion. METHODS: Following Institutional Review Board approval, all female patients who underwent robotic cystectomy for rUTI between 2011 and 2021 were identified from a prospectively-maintained internal database at a tertiary care center. Exclusion criteria included interstitial cystitis, neurogenic bladder, urinary tract neoplasm, or congenital abnormality. Electronic medical records were reviewed by an independent researcher. Patients were also administered the Quality of Life Questionnaire-C30. RESULTS: Twenty-four patients met inclusion criteria. Median age was 75 years (range 53-87). Median rUTI duration was 6 (interquartile range [IQR] 2-10) years. Median urinary tract infections count in the 12-month preceding cystectomy was 5 (IQR 3-9). Infections with multidrug resistant organisms were found in 21 patients (88%). The 30-day postoperative complication rate was 79% (19/24), of which 11% were Clavien-Dindo grade ≥III. The main late complication was parastomal hernia, with 17% requiring repair or revision. At a median of 36 months (range 12-61) post-operatively, the median Quality of Life Questionnaire-C30 global health status score was 50 (range 33-83). CONCLUSION: Cystectomy is a last-resort management option for women with severely symptomatic end-stage bladders in the setting of antibiotic-recalcitrant rUTI. Patients should be counseled thoroughly regarding possible acute and long-term postoperative complications. Select patients, managed in high-volume referral centers, can benefit from robotic simple cystectomy with ileal conduit urinary diversion.	bladder
Urinary and household chemical exposures in pet dogs with urothelial cell carcinoma.	Urothelial cell carcinoma (UCC) has been linked to environmental chemical exposures in people, but these risk factors are not well understood in dogs with UCC. We hypothesised that household chemical exposures contribute to the risk of UCC in pet dogs. This prospective cross-sectional case-control study included 37 dogs with UCC and 37 unaffected breed-, sex-, and age-matched controls. Dog owners completed an environmental questionnaire and household samples were collected and analysed for arsenic (in tap water and room dust) and acrolein (in room air). Urine samples from UCC dogs, control dogs, and consenting owners were analysed for inorganic arsenic species, the acrolein metabolite 3-HPMA, and the phenoxy herbicide 2,4-D. Public data on chlorination byproducts (total trihalomethanes) in municipal drinking water were also compared between case and control households. Dogs with UCC were more likely to swim in a pool (15.2%) compared with control dogs (0%) (OR 1.69, 95% CI = 1.69-∞; p = .02). Dogs with UCC also had more than 4-fold higher reported municipal water concentrations of chlorination byproducts (median 28.0 ppb) compared with controls (median 6.9 ppb; p < .0001). Dust arsenic concentrations were unexpectedly lower in case households (median 0.277 ng/cm(2)) compared with control households (median 0.401 ng/cm(2); p = .0002). Other outcomes were not significantly different between groups. These data suggest that dog owners, especially those of breeds known to be at higher risk for UCC, consider limiting access to swimming pools and installing water filtration units that remove total trihalomethanes.	bladder
METTL16 suppressed the proliferation and cisplatin-chemoresistance of bladder cancer by degrading PMEPA1 mRNA in a m6A manner through autophagy pathway.	N6-methyladenosine (m6A) is important in the physiological processes of many species. Methyltransferase-like 16 (METTL16) is a novel discovered m6A methylase, regulating various tumors in an m6A-dependent manner. However, its function in bladder cancer (BLCA) remains largely unclear. In the present study, we found that low expression of METTL16 predicted poor survival in BLCA patients. METTL16 inhibited the proliferation and cisplatin-resistance function of bladder cancer cells in vitro and in vivo. In addition, METTL16 reduced the mRNA stability of prostate transmembrane protein androgen induced-1 (PMEPA1) via binding to its m6A site in the 3'-UTR, thereby inhibited the proliferation of bladder cancer cells and increased the sensitivity of cisplatin through PMEPA1-mediated autophagy pathway. Finally, we found that hypoxia-inducible factor 2α (HIF-2α) exerted its tumor-promoting effect by binding the METTL16 promoter region to repress its transcription. Taken together, High expression of METTL16 predicted better survival in BLCA. METTL16 significantly inhibited bladder cancer cell proliferation and sensitized bladder cancer cells to cisplatin via HIF-2α-METTL16-PMEPA1-autophagy axis in a m6A manner. These findings might provide fresh insights into BLCA therapy.	bladder
Prognostic Impact and Spatial Interplay of Immune Cells in Urothelial Cancer.	"BACKGROUND AND OBJECTIVE: Quantity and the spatial relationship of specific immune cell types can provide prognostic information in bladder cancer. The objective of the study was to characterize the spatial interplay and prognostic role of different immune cell subpopulations in bladder cancer. METHODS: A total of 2463 urothelial bladder carcinomas were immunostained with 21 antibodies using BLEACH&STAIN multiplex fluorescence immunohistochemistry in a tissue microarray format and analyzed using a framework of neuronal networks for an image analysis. Spatial immune parameters were compared with histopathological parameters and overall survival data. KEY FINDINGS AND LIMITATIONS: The identification of > 300 different immune cell subpopulations and the characterization of their spatial relationship resulted in numerous spatial interaction patterns. Thirty-nine immune parameters showed prognostic significance in univariate analyses, of which 16 were independent from pT, pN, and histological grade in muscle-invasive bladder cancer. Among all these parameters, the strongest association with prolonged overall survival was identified for intraepithelial CD8(+) cytotoxic T cells (time-dependent area under receiver operating characteristic curve [AUC]: 0.70), while stromal CD8(+) T cells were less relevant (AUC: 0.65). A favorable prognosis of inflamed cancers with high levels of ""exhaustion markers"" suggests that TIM3, PD-L1, PD-1, and CTLA-4 on immune cells do not hinder antitumoral immune response in tumors rich of tumor infiltrating immune cells. CONCLUSIONS AND CLINICAL IMPLICATIONS: The density of intraepithelial CD8(+) T cells was the strongest prognostic feature in muscle-invasive bladder cancer. Given that tumor cell killing by CD8(+) cytotoxic T lymphocytes through direct cell-to-cell-contacts represents the ""terminal end route"" of antitumor immunity, the quantity of ""tumor cell adjacent CD8(+) T cells"" may constitute a surrogate for the efficiency of cancer recognition by the immune system that can be measured straightaway in routine pathology as the CD8 labeling index. PATIENT SUMMARY: Quantification of intraepithelial CD8(+) T cells, the strongest prognosticfeature identified in muscle-invasive bladder cancer, can easily be assessed by brightfield immunohistochemistry and is therefore ""ready to use"" for routine pathology."	bladder
Blood-based liquid biopsy: A promising noninvasive test in diagnosis, surveillance, and prognosis of patients with upper tract urothelial carcinoma.	OBJECTIVES: To assess the efficacy of blood-based liquid biopsy in the diagnosis, surveillance, and prognosis of upper tract urothelial carcinoma (UTUC). METHODS AND MATERIALS: In this prospective study, peripheral blood samples were collected from patients with primary UTUC before surgery with curative intent and follow-up visits at University of Southern California between May 2021 and September 2022. The samples were analyzed using the third-generation comprehensive high-definition single-cell assay (HDSCA3.0) to detect rare events, including circulating tumor cells (CTCs) and oncosomes, based on the immunofluorescence signals of DAPI (D), cytokeratin (CK), CD45/CD31 (CD), and vimentin (V). The findings of pre-surgery liquid biopsies were compared with those of blood samples from normal donors (NDs) and matched follow-up liquid biopsies. The association between liquid biopsy findings and clinical data, including recurrence-free survival (RFS), was also assessed. RESULTS: Twenty-eight patients with UTUC were included, of whom 21 had follow-up samples. Significant differences in specific rare analytes were detected in the preoperative samples compared to the NDs. In the post- vs. presurgery matched analysis, a significant decrease was detected in total-, CK-, and CK|V oncosomes, as well as in D-, D|V-, and D|V|CD cells. With a median follow-up of 11 months, 8 patients had disease recurrence. Survival analysis demonstrated that patients with >1.95 preoperative CK|V oncosomes (p = 0.020) and those with >4.18 D|CK|V cells (p = 0.050) had worse RFS compared to other patients. CONCLUSIONS: This study demonstrated promising initial evidence for the biomarker role of CTCs and oncosomes in the diagnosis and surveillance of patients with UTUC.	bladder
Clinical significance of blocking novel immune checkpoint B7-H4 in urothelial carcinoma of bladder as a potential therapeutic target.	Urothelial Carcinoma of Bladder is complex disease with high mortality and recurrence rates. Current standard regimes have exhibited anti-tumor activity but still, a proportion of patients are non-responsive or in-eligible to receive such treatments. Immune checkpoints have emerged as potential class of therapeutics to be tested in UCB patients. Clinical trials targeting PD-1/PD-L1 axis have been tested in UCB but still a proportion of patients are non-responsive to it which stresses upon identifying new targets. New immune checkpoint B7-H4 has been shown to negatively regulate T cell activity in cancer and is a poor prognostic factor in various solid tumors. In this study we assessed the novel immune checkpoint B7-H4 status in UCB patients. We observed elevated expression of B7-H4 and PD-L1 on CD8+ T cells in circulation of UCB patients. Relative mRNA expression and immunohistochemistry displayed upregulation in bladder tumor tissue. Increased expression of B7-H4 along with PD-L1 in periphery and tumor of UCB patients highlights involvement of B7-H4 in disease progression. Combinatorial blocking of B7-H4 and PD-L1 enhanced IFN-γ and granzyme B in CD8+ T cells functional T cell immune response in UCB patients. Also, B7-H4 was significantly associated with clinico-pathological parameters. Our findings highlight B7-H4 as potential therapeutic target for treatment of UCB patients in future after further validation.	bladder
Ivermectin Inhibits Bladder Cancer Cell Growth and Induces Oxidative Stress and DNA Damage.	BACKGROUND: Bladder cancer is the most common malignant tumor of the urinary system. Nevertheless, current therapies do not provide satisfactory results. It is imperative that novel strategies should be developed for treating bladder cancer. OBJECTIVES: To evaluate the effect of a broad-spectrum anti-parasitic agent, Ivermectin, on bladder cancer cells in vitro and in vivo. METHODS: CCK-8 and EdU incorporation assays were used to evaluate cell proliferation. Apoptosis was detected by flow cytometry, TUNEL assay, and western blotting. Flow cytometry and DCFH-DA assay were used to analyze the reactive oxygen species (ROS) levels. DNA damage was determined by Neutral COMET assay and γ H2AX expression. Proteins related to apoptosis and DNA damage pathways were determined by WB assay. Xenograft tumor models in nude mice were used to investigate the anti-cancer effect of Ivermectin in vivo. RESULTS: Our study showed that in vitro and in vivo, Ivermectin inhibited the growth of bladder cancer cells. In addition, Ivermectin could induce apoptosis, ROS production, DNA damage, and activate ATM/P53 pathwayrelated proteins in bladder cancer cells. CONCLUSIONS: According to these findings, Ivermectin may be a potential therapeutic candidate against bladder cancer due to its significant anti-cancer effect.	bladder
HER2 Affects the Biological Behaviours of Bladder Cancer Cells and is Closely Associated with the Progression and Prognosis of Bladder Cancer.	OBJECTIVE: Given the growing recognition of molecular targets in oncology, this study aimed to examine the expression pattern and prognostic significance of human epidermal growth factor receptor-2 (HER2) in bladder cancer (BC) and the effects of HER2 knockdown on the biological behaviours of BC cells. METHODS: A total of 126 BC tissue samples and 20 samples of normal bladder mucosa were collected for immunohistochemical staining. The clinicopathological data were obtained from patients with BC. HER2 was knocked down in two BC cell lines (T24 and 5637) using lentiviral delivery of short hairpin RNA (shRNA), referred to as shHER2, with a blank control group (shCtrl) for comparison. A range of assays, including cell counting kit-8, colony formation, transwell, wound healing, and flow cytometry, were performed to assess the effects of HER2 knockdown on the proliferation, migration, cell cycle entry, and apoptosis of BC cells. RESULTS: The study revealed a notable overexpression rate of HER2 in BC tissues (57.1%) than in normal bladder mucosa (0%) (p < 0.001). HER2 overexpression was associated with tumour number (p < 0.0001), pathological grade (p < 0.0001), lymph node metastasis (p = 0.040), distant metastasis (p = 0.037), overall survival (p = 0.0006), and recurrence-free survival (RFS) (p < 0.0001). In contrast, no significant association was identified between HER2 overexpression and demographic factors such as sex (p = 0.687), age (p = 0.430), tumour size (p = 0.053), or T stage (p = 0.134). Furthermore, the experimental knockdown of HER2 in BC cells inhibited the proliferation and migration and promoted their apoptosis and cell cycle arrest in the G1 phase. CONCLUSIONS: The findings suggest HER2 as a potential therapeutic target for BC and underscore the promise of developing anti-HER2-targeting strategies for BC management.	bladder
Comparison of narrow band imaging versus white light imaging in detecting non muscle invasive bladder cancer.	BACKGROUND: In the present study, we compared Narrow Band Imaging (NBI) and White Light Cystoscopy (WLC) in Non-muscle invasive bladder cancer (NMIBC) for detection and its impact on recurrence. MATERIALS AND METHODS: This prospective study was conducted in the department of Urology at a tertiary institution from August 2021 to April 2023. The main aim was to determine the benefit of addition of NBI during TURBT in NMIBC. All patients with Urinary Bladder Mass (size less than 5 cm on USG/CT) aged >18 years of age planned for TURBT were included. RESULTS: Amongst 63 patients, the mean age was 59.84 ± 11.3 years; 80% were males. Sixty percent of patients had history of Tobacco consumption and Type II DM was the most common comorbidity (59%). Commonest symptom was gross haematuria. Posterior wall was most commonly involved and papillary lesions were commonest. A total of 125 lesions were identified on WLI, with mean 1.98 ± 1.75 and 78 additional lesions were identified only on NBI with mean 1.24 ± 1.63 lesions. Four patients had intra-operative complications. Five patients had recurrence at 6 weeks and eight patients had recurrence at 3 months. NBI had detected more lesions in patients who developed recurrence at 6 weeks and 3 months (mean: 1.41 and 1.43). CONCLUSION: NBI has additive role in detecting NMIBC lesions missed on WLI. NBI has significant role in preventing recurrence at 3 months and more so by detecting high grade tumours.	bladder
Systemic Inflammatory Index: A Promising Non-Invasive Marker for the Prediction of Response to Neoadjuvant Chemotherapy prior to Cystectomy.	INTRODUCTION: The main challenge to the optimal use of neoadjuvant chemotherapy (NAC) is the difficulty in selecting patients who may or may not benefit from NAC. Our aim in this study was to investigate whether the Systemic Inflammatory Index (SII) predicts response to chemotherapy in patients who receive NAC prior to cystectomy. METHODS: We retrospectively analysed the data of patients who underwent NAC followed by cystectomy at our institution between January 2010 and September 2015 and whose 5-year follow-up was completed. All patients who underwent diagnostic biopsy with complete transurethral resection of bladder tumour at our hospital and whose pathology result was muscle-invasive transitional cell carcinoma were included in the study. At least 3 courses of gemcitabine/cisplatin NAC were given to all patients. A pathological response was defined as a reduction in cystectomy to a lower pathological stage after NAC. RESULTS: The SII was 320.8 ± 51 in the responders and 388.28 ± 50 in the non-responders. SII optimal cut-off of 350 was determined. The sensitivity and specificity of SII in predicting response were found to be 80% and 83%, respectively. Low SII (&lt;350) was found to be a significant predictor of response compared with the other factors on multivariate analysis. The mean overall survival time was 55.4 months in patients with a low SII value and 40.3 months in the high SII group. CONCLUSION: SII, together with known clinicopathological factors and newer genetic and molecular markers, can be used to select patients for NAC.	bladder
Occupational exposure to organic solvents and risk of bladder cancer.	BACKGROUND: Bladder cancer has been linked to several occupations that involve the use of solvents, including those used in the dry-cleaning industry. OBJECTIVES: We evaluated exposure to solvents and risk of bladder cancer in 1182 incident cases and 1408 controls from a population-based study. METHODS: Exposure to solvents was quantitatively assessed using a job-exposure matrix (CANJEM). Exposure to benzene, toluene and xylene often co-occur. Therefore, we created two additional sets of metrics for combined benzene, toluene and xylene (BTX) exposure: (1) CANJEM-based BTX metrics and (2) hybrid BTX metrics, using an approach that integrates the CANJEM-based BTX metrics together with lifetime occupational histories and exposure-oriented modules that captured within-job, respondent-specific details about tasks and chemicals. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CI) were estimated using logistic regression. RESULTS: Bladder cancer risks were increased among those ever exposed to benzene (OR = 1.63, 95% CI: 1.14-2.32), toluene (OR = 1.60, 95% CI: 1.06-2.43), and xylene (OR = 1.67, 95% CI: 1.13-2.48) individually. We further observed a statistically significant exposure-response relationship for cumulative BTX exposure, with a stronger association using the hybrid BTX metrics (OR(Q1vsUnexposed) = 1.26, 95% CI: 0.83-1.90; OR(Q2vsUnexposed) = 1.52, 95% CI: 1.00-2.31; OR(Q3vsUnexposed) = 1.88, 95% CI: 1.24-2.85; and OR(Q4vsUnexposed) = 2.23, 95% CI: 1.35-3.69) (p-trend=0.001) than using CANJEM-based metrics (p-trend=0.02). IMPACT: There is limited evidence about the role of exposure to specific organic solvents, alone or in combination on the risk of developing bladder cancer. In this study, workers with increasing exposure to benzene, toluene, and xylene as a group (BTX) had a statistically significant exposure-response relationship with bladder cancer. Future evaluation of the carcinogenicity of BTX and other organic solvents, particularly concurrent exposure, on bladder cancer development is needed.	bladder